{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:27:07Z","timestamp":1792805227111,"version":"4.5.0"},"reference-count":192,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundaci\u00f3n \u201cAlfonso X el Sabio\u201d-Banco Santander, Spain","award":["1.400.001"],"award-info":[{"award-number":["1.400.001"]}]},{"name":"Biobanco Hospital Universitario Fundaci\u00f3n Alcorc\u00f3n","award":["1.400.001"],"award-info":[{"award-number":["1.400.001"]}],"id":[{"id":"https:\/\/ror.org\/01435q086","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The dentate gyrus (DG) of the human hippocampus is a complex and dynamic structure harboring mature and immature granular neurons in diverse proliferative states. While most mammals show persistent neurogenesis through adulthood, human neurogenesis is still under debate. We found nuclear alterations in granular cells in autopsied human brains, detected by immunohistochemistry. These alterations differ from those reported in pyramidal neurons of the hippocampal circuit. Aging and early AD chromatin were clearly differentiated by the increased epigenetic markers H3K9me3 (heterochromatin suppressive mark) and H3K4me3 (transcriptional euchromatin mark). At early AD stages, lamin B2 was redistributed to the nucleoplasm, indicating cell-cycle reactivation, probably induced by hippocampal nuclear pathology. At intermediate and late AD stages, higher lamin B2 immunopositivity in the perinucleus suggests fewer immature neurons, less neurogenesis, and fewer adaptation resources to environmental factors. In addition, senile samples showed increased nuclear Tau interacting with aged chromatin, likely favoring DNA repair and maintaining genomic stability. However, at late AD stages, the progressive disappearance of phosphorylated Tau forms in the nucleus, increased chromatin disorganization, and increased nuclear autophagy support a model of biphasic neurogenesis in AD. Therefore, designing therapies to alleviate the neuronal nuclear pathology might be the only pathway to a true rejuvenation of brain circuits.<\/jats:p>","DOI":"10.3390\/ijms232112873","type":"journal-article","created":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T22:00:27Z","timestamp":1666735227000},"page":"12873","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Pathological Nuclear Hallmarks in Dentate Granule Cells of Alzheimer\u2019s Patients: A Biphasic Regulation of Neurogenesis"],"prefix":"10.3390","volume":"23","author":[{"given":"Laura","family":"Gil","sequence":"first","affiliation":[{"name":"Facultad de Medicina, Universidad Alfonso X el Sabio (UAX), Avenida de la Universidad, 1, 28691 Villanueva de la Ca\u00f1ada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Chi-Ahumada","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Facultad de Medicina, Universidad Aut\u00f3noma de San Luis Potos\u00ed, Av. Venustiano Carranza 2405, San Luis Potos\u00ed 78210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7665-2468","authenticated-orcid":false,"given":"Sandra A.","family":"Ni\u00f1o","sequence":"additional","affiliation":[{"name":"Geroscience Center for Brain Health and Metabolism (GERO), Santiago de Chile 7750000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Capdeville","sequence":"additional","affiliation":[{"name":"Escuela de Medicina, Universidad Panamericana, Ciudad de Mexico 03920, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Areli M.","family":"M\u00e9ndez-Torres","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Facultad de Medicina, Universidad Aut\u00f3noma de San Luis Potos\u00ed, Av. Venustiano Carranza 2405, San Luis Potos\u00ed 78210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Guerrero","sequence":"additional","affiliation":[{"name":"Banco de Cerebros (Biobanco), Hospital Universitario Fundaci\u00f3n Alcorc\u00f3n, 28922 Alcorc\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3151-7999","authenticated-orcid":false,"given":"Ana B.","family":"Rebolledo","sequence":"additional","affiliation":[{"name":"Banco de Cerebros (Biobanco), Hospital Universitario Fundaci\u00f3n Alcorc\u00f3n, 28922 Alcorc\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6579-0328","authenticated-orcid":false,"given":"Isabel M.","family":"Olazabal","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad Alfonso X el Sabio (UAX), Avenida de la Universidad, 1, 28691 Villanueva de la Ca\u00f1ada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8342-7063","authenticated-orcid":false,"given":"Mar\u00eda E.","family":"Jim\u00e9nez-Capdeville","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica, Facultad de Medicina, Universidad Aut\u00f3noma de San Luis Potos\u00ed, Av. Venustiano Carranza 2405, San Luis Potos\u00ed 78210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1749-6632.2001.tb05830.x","article-title":"Plasticity of the hippocampus: Adaptation to chronic stress and allostatic load","volume":"933","author":"McEwen","year":"2001","journal-title":"Ann. N. Y. Acad. 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